Project Abstract/Summary: Cervical cancer screening programs remain essential to reduce cervical cancer in women despite the availability of human papilloma virus (HPV) vaccines. Screening is important for all women but is particularly important for women living with HIV given the high prevalence of HPV in this group and risks associated with progression notwithstanding antiretroviral therapy. Here we propose to investigate the clinical utility of a new method of automated digital imaging of the cervix on the MobileODT platform as a screen-and-treat approach. We build on a long-term collaboration between the University of Cape Town and Columbia University investigating how to strengthen cervical cancer screening and treatment in South Africa. Currently, screen-and-treat programs utilizing HPV DNA testing are recommended by the World Health Organization. We have demonstrated the safety, efficacy and cost-effectiveness of this approach for the South African setting with its high HIV prevalence in women. In this setting, we are currently completing an NCI- supported study demonstrating the feasibility and outstanding performance of an HPV DNA assay that can be used at the point-of-care for a single-visit, screen-and-treat program. Here we propose to extend this work to investigate in Specific Aim 1: the performance characteristics of automated digital imaging as a standalone, primary screening test to replace HPV DNA testing for use in the single-visit, screen-and-treat approach; Specific Aim 2: the performance characteristics of automated digital imaging as a triage test for women who test HPV DNA positive in the screen- and-treat approach; and Specific Aim 3: facility-level operational challenges and facilitators to integrating this new imaging technology into single-visit screen-and-treat programs. We propose to undertake the studies to address these aims among women living with and without HIV at clinical sites in Cape Town, South Africa. Our overall goal is to strengthen cervical cancer screening approaches to reduce cost and improve the effectiveness of screening.